Advent of genetic engineering made small rodents a powerful platform for investigation of the genetic foundation of normal and pathological cardiovascular physiology. Through these studies, primarily in mice, many cardiovascular diseases have been linked to a particular protein or group of molecules in the heart or nervous system. Large animals are used to study heart rhythm disorders associated with abnormally high rate achieved by rapid pacing of the atria or ventricles, and which results in heart failure and atrial fibrilation. Unfortunately, genetic engineering of large animals is not available or prohibitively expensive, which limits our ability to study the molecular basis of cardiovascular disease in these animals. In contrast, unlike large animal models, chronic studies in mouse and other small mammals are limited due to our inability to stimulate the heart and nerves. The size of existing pacemakers is a limiting factor, and prevents us from extending electronic implantable devices to studies of heart rhythm disorders in genetically engineered mice. Thus, there is an unmet need to combine genetic engineering in small rodents with implantable device technology for heart rhythm control. In this project, we propose to develop an implantable programmable miniature pacemaker, which can be used in mouse and other species for long-term chronic pacing at desired rate and pulse durations. We will use state- of-the-art electrical engineering technology to create a miniature implantable device. Successful completion of this project will allow bridging the gap between two state of the art technologies: (1) genetic engineering of the mouse and (2) implantable device technology for heart rhythm control. Combination of these two technologies will allow investigation of molecular mechanisms responsible for heart rhythm disorders and heart failure secondary to rapid rate. These studies will advance pre-clinical research of arrhythmia and heart failure. In the future we also plan to extend this technology to both pacing and sensing the cardiac electrical activity. PUBLIC HEALTH RELEVANCE: Genetic engineering of large animals is not available or prohibitively expensive, which limits our ability to study the molecular basis of cardiovascular disease in these animals. In contrast, unlike large animal models, chronic studies in mouse and other small mammals are limited due to our inability to stimulate the heart and nerves. The size of existing pacemakers is a limiting factor, and prevents us from extending electronic implantable devices to studies of heart rhythm disorders in genetically engineered mice. In this project, we propose to develop an implantable programmable miniature pacemaker, which can be used in mouse and other species for long-term chronic pacing at desired rate and pulse durations. We will use state-of-the-art electrical engineering technology to create a miniature implantable device.